A plain language summary of the safety of relugolix combination therapy and improvement in symptoms in women with uterine fibroids from the LIBERTY 1 and LIBERTY 2 studies.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of research studies (known as clinical trials) called LIBERTY 1 and LIBERTY 2. The LIBERTY 1 and LIBERTY 2 studies looked at how well a medication called relugolix combination therapy worked to reduce heavy bleeding at the time of menstruation compared with placebo. The studies also looked at what side effects were reported in women with uterine fibroids and heavy menstrual bleeding. WHAT WERE THE RESULTS?: Researchers looked at 388 adult women in the LIBERTY 1 study and 382 adult women in the LIBERTY 2 study. All women had heavy menstrual bleeding with uterine fibroids before the start of the LIBERTY 1 and LIBERTY 2 studies. The women were given one of three treatments during the studies: relugolix combination therapy or placebo for 24 weeks, or delayed relugolix combination therapy (relugolix alone for the first 12 weeks, then relugolix combination therapy for the last 12 weeks of the studies). More women taking relugolix combination therapy in the LIBERTY 1 study (73%) and LIBERTY 2 study (71%) had menstrual blood loss of less than one-third of a cup (80 mL) and had reduction of at least 50% less blood loss during their last menstrual period after 24 weeks of taking the medicine compared with placebo (LIBERTY 1: 19% and LIBERTY 2: 15%). The women taking relugolix combination therapy also had less pain than those taking placebo. Side effects were similar across treatment groups. Headaches and hot flushes were the most common side effects. WHAT DO THE RESULTS MEAN?: More women with uterine fibroids taking relugolix combination therapy for 24 weeks were likely to have fewer uterine fibroid symptoms than women receiving placebo. Clinical Trial Registration: NCT03049735 (LIBERTY 1); NCT03103087 (LIBERTY 2).

Chronic pelvic pain in women: an embedded qualitative study to evaluate the perceived benefits of the meridian balance method electro-acupuncture treatment, health consultation and National Health Service standard care.

INTRODUCTION: Chronic pelvic pain (CPP) - defined as intermittent or constant pain in the lower abdomen or pelvis of at least 6 months' duration, not occurring exclusively with menstruation or intercourse and not associated with pregnancy - is estimated to affect 6-27% of women worldwide. In the United Kingdom, over 1 million women suffer from CPP, which has been highlighted as a key area of unmet need. Current medical treatments for CPP are often associated with unacceptable side effects. A specific style of acupuncture, the meridian balance method electro-acupuncture (BMEA) and traditional Chinese medicine health consultation (TCM HC (BMEA + TCM HC = BMEA treatment)), may be effective for CPP in women. AIM: Three focus group discussions and semi-structured telephone interviews were embedded in a randomised controlled feasibility trial to gain in-depth description of the perceived benefits of the participants' respective interventions. METHODS: Women with CPP were randomised into the BMEA treatment, TCM HC or National Health Service standard care (NHS SC). Focus group discussions were recorded, transcribed and analysed thematically. Semi-structured telephone interviews were conducted post focus group discussions. FINDINGS: A total of 30 women were randomised into BMEA treatment, TCM HC or NHS SC. A total of 11 participants attended the three focus group discussions. Thematic analysis of focus group discussions showed: a perceived pain reduction, enhanced sleep, energy level and sense of well-being in the BMEA treatment and TCM HC groups; a dislike for the adverse effects of medications, frustration at the lack of effective treatment, heavy reliance on medications and services that are helpful, in the NHS SC group. Semi-structured telephone interviews showed that the methodology was acceptable to the participants. CONCLUSION: The embedded focus group discussions captured the rich and complex narratives of the participants and provided insights into the perceived benefits of the BMEA treatment, TCM HC and NHS SC interventions.

The impact of meridian balance method electro-acupuncture treatment on chronic pelvic pain in women: a three-armed randomised controlled feasibility study using a mixed-methods approach.

INTRODUCTION: Chronic pelvic pain (CPP) is estimated to affect 6%-27% of women worldwide. In the United Kingdom, over 1 million women suffer from CPP and it has been highlighted as a key area of unmet need. Standard treatments are associated with unacceptable side effects. The meridian balance method electro-acupuncture (BMEA), and traditional Chinese medicine health consultation (TCM HC) (BMEA + TCM HC = BMEA treatment) may be an effective adjunct to standard treatment. AIM: The aim of our study was to evaluate the feasibility of a future trial, to determine the effectiveness of the BMEA treatment for CPP in women. The primary objectives were to determine recruitment and retention rates. The secondary objectives were to assess the effectiveness of the BMEA treatment and acceptability of the study's methodology. METHODS: Women with CPP were randomised into BMEA treatment (group 1), TCM HC alone (group 2) (each intervention administered twice weekly for 4 weeks) or National Health Service standard care (NHS SC, group 3). Primary outcomes were assessed by the proportion of eligible participants randomised, and the proportion of randomised participants who returned follow-up questionnaires. Interventions were assessed by validated pain/physical/emotional functioning questionnaires at baseline (0), 4, 8 and 12 weeks. Focus groups and semi-structured telephone interviews were embedded in the study. RESULTS: A total of 30 women (51% of those referred) were randomised over 8 months. Retention rates were 80% (95% confidence interval (CI): 74-96), 53% (95% CI: 36-70) and 87% (95% CI: 63-90), in groups 1, 2, and 3, respectively. Qualitative data suggested a favourable trial experience in groups 1 and 3. DISCUSSION: Group 2 retention rate was problematic and has implications for our next trial. CONCLUSION: Our study suggests that a future trial to determine the effectiveness of BMEA treatment for women with CPP is feasible but with modifications to the study design.

Development of a Bayesian response-adaptive trial design for the Dexamethasone for Excessive Menstruation study.

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. This article describes the preparatory simulation study for a Bayesian response-adaptive dose-finding trial design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of Dexamethasone in reducing excessive menstrual bleeding and to determine the best dose for further study. To maximise learning about the dose response, patients receive placebo or an active dose with randomisation probabilities adapting based on evidence from patients already recruited. The dose-response relationship is estimated using a flexible Bayesian Normal Dynamic Linear Model. Several competing design options were considered including: number of doses, proportion assigned to placebo, adaptation criterion, and number and timing of adaptations. We performed a fractional factorial study using SAS software to simulate virtual trial data for candidate adaptive designs under a variety of scenarios and to invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial results using Normal linear models to estimate the effects of each design feature on empirical type I error and statistical power. Our readily-implemented approach using widely available statistical software identified a final design which performed robustly across a range of potential trial scenarios.

Advances in the management of uterine fibroids.

Uterine fibroids are extremely common, with major surgery the current main management option; uterine artery embolisation is an alternative, but risks to fertility are unclear. Minimally invasive procedures are becoming more commonly performed via both the hysteroscope and laparoscope, minimising recovery time for patients. Recently, small doses of progesterone receptor modulators (mifepristone and asoprisnil) have been shown to be effective in reducing menstrual blood loss and fibroid size. Progress from here should include the development of a well-tolerated oral preparation that will maintain fertility.

Abnormal uterine bleeding: getting our terminology straight.

PURPOSE OF REVIEW: This review highlights the difficulties currently caused by the ill-defined and confused use of terminologies to describe symptoms, signs and causes of abnormal uterine bleeding. It also attempts to put usage of modern terminologies in an historical context with important lessons for current usage. RECENT FINDINGS: Confused terminology has led to difficulties in interpreting the results of many clinical trials of new therapies and surgical procedures for abnormal uterine bleeding, and in understanding some studies investigating underlying mechanisms of bleeding. The confusion is so great that a major international expert group has recommended abolition of such terms as 'menorrhagia', 'metrorrhagia' and 'dysfunctional uterine bleeding', and replacement with much simpler terms to specifically cover cycle regularity, frequency, duration and heaviness of bleeding episodes, and to acknowledge a significant change in pattern for individual women. New terminologies are required to describe certain underlying causes of abnormal uterine bleeding. SUMMARY: Such discussion should be an ongoing process aimed towards good international agreement, which will greatly simplify the interpretation of clinical trials and scientific studies of mechanisms and treatment responses, and will contribute to the process of education at all levels.